Rabbit pulmonary monooxygenase system: catalytic differences between two purified forms of cytochrome P-450 in the metabolism of benzo(a)pyrene

Journal Article · Thu May 10 00:00:00 EDT 1979 · J. Biol. Chem.; (United States)

OSTI ID:5338260

Wolf, C R; Smith, B R; Ball, L M; Serabjit-Singh, C; Bend, J R; Philpot, R M

The metabolism and activation of the pulmonary carcinogen, benzo(a)pyrene, have been examined in reconstituted rabbit pulmonary monooxygenase systems. Two forms of purified pulmonary cytochrome P-450, which are known to have different monomeric molecular weights, spectral properties, and substrate specificities, were compared. Metabolite profiles were obtained using high pressure liquid chromatography. Metabolites that chromatographed with the 3-hydroxy and quinone standards accounted for 95% of the total activity of cytochrome I. With cytochrome II metabolism at positions 9 and 10 accounted for 40 to 50% of the total activity; products that chromatographed with the 3-hydroxy standard were 30 to 40% of the total. Formation of the 4,5- or 7,8-dihydrodiol metabolites accounted for less than 5% of the total produced by either cytochrome. The metabolism of benzo(a)pyrene by cytochrome II was inhibited by ..cap alpha..-naphthoflavone (K/sub i/ = 8.2 +- 0.4 x 10/sup -9/ M) in a manner that did not affect the profile of the metabolites produced. Metabolism by cytochrome I was not significantly inhibited by ..cap alpha..-naphthoflavone at a concentration of 10/sup -4/ M. Cytochrome II, unlike cytochrome I, catalyzed the metabolism of benzo(a)pyrene to products that bound covalently to DNA. The involvement of the two pulmonary cytochromes in the formation of potentially carcinogenic metabolites from benzo(a)pyrene is discussed.

• Research Organization: National Inst. of Environmental Health Sciences, Research Triangle Park, NC
• OSTI ID: 5338260
• Journal Information: J. Biol. Chem.; (United States), Vol. 254:9
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
BENZOPYRENE
METABOLISM
CYTOCHROMES
ENZYME ACTIVITY
METABOLITES
TOXICITY
BIOCHEMICAL REACTION KINETICS
COMPARATIVE EVALUATIONS
DNA
ENZYME INHIBITORS
LUNGS
RABBITS
ANIMALS
AROMATICS
BODY
CONDENSED AROMATICS
HYDROCARBONS
KINETICS
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PIGMENTS
REACTION KINETICS
RESPIRATORY SYSTEM
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
550200 - Biochemistry